The current exploration of alternative fuels to conventional engines is tested on two fronts: the thermophysical property assessment and the other, real-time evaluation using engine testing using the fuel. The engine testing fueled with modified oils/esterified blends does give real-time analysis but at the cost of harmful emissions dumped into the polluted environment. The current work describes the use of possible simulations and the validity of simulation confirmed from real-time experimentation at varying engine compression ratios (CRs). Engine parameters were kept the same for simulations that were performed on the Diesel RK module and experimental analysis.Neem oil blends were prepared and tested for the composition of FFA and later the required properties were supplemented to software for possible thermal performance and emission detections. The thermal efficiency deviation observed between RK model and experimental values for CR 18 for Diesel, B20, B40, and Heat Transfer. 2022;51:7990-8004. wileyonlinelibrary.com/journal/htj B100 was 5.8%, 1.9%, 3.4%, and 2.1%, respectively, and for NOx, the deviation observed for Diesel, B20, B40, and B100 was 8.9% and 13.7%, 12.2% and 14.1%, and 9.4% and 11.1%, respectively. The peak HRR and cylinder pressures observed for software simulations and real-time experimental approaches did not vary much, but the peak values do differ by 6.7% and 4.7%, respectively.